A 11 MB YAC-BASED CONTIG SPANNING THE FAMILIAL JUVENILE NEPHRONOPHTHISIS REGION (NPH1) LOCATED ON CHROMOSOME 2Q

A gene (NPH1) responsible for approximately 90% of the purely renal fo rm of familial juvenile nephronophthisis, a progressive tubulo-interst itial kidney disorder, maps to human chromosome 2, We report the const ruction of a YAC-based contig spanning the critical NPH1 region and th e flanking genetic markers, This physical map was integrated with a re fined genetic map that restricted the NPH1 interval to about 2 cM; thi s interval corresponds to a maximum physical distance of 3.5 Mb, The e ntire contig covers 9 cM between the loci D2S135 and D2S121, The maxim um physical distance between these two markers is approximately 11.3 R ib. Forty-five sequence-tagged sites, including six genes, have been l ocated within this contig, PAX8, a member of the human paired box gene family, that is expressed in the developing kidney, was assigned outs ide the restricted NPH1 critical region and cannot therefore be regard ed as a candidate gene, This set of overlapping clones represents a us eful resource for further targeted development of genetic markers and for the characterization of candidate genes responsible for juvenile n ephronophthisis. (C) 1995 Academic Press, Inc.